Skin biopsy samples from the fingers of nine patients with primary Raynaud's phenomenon, nine with the disorder associated with systemic sclerosis, and eleven healthy controls were examined by immunocytochemistry. There were no differences between the groups in the distribution of PGP 9.5 (a pan-neuronal marker) immunoreactivity, but there was a significant reduction in the number of calcitonin gene-related peptide (CGRP) immunoreactive neurons in the skin of patients with primary Raynaud's phenomenon and those with systemic sclerosis. These findings implicate dysfunction of the CGRP neurovascular axis in the pathophysiology of Raynaud's phenomenon.